Common polymorphisms in GSTM1, GSTT1, GSTP1, GSTA1 and susceptibility to colorectal cancer in the Central European population

Hezova Renata, Bienertova-Vasku Julie, Sachlova Milana, Brezkova Veronika, Vasku Anna, Svoboda Marek, Radová Lenka, Kiss Igor, Vyzula Rostislav, Slaby, Slaby Ondrej

Description

Central Europe presents with the highest incidence of sporadic colorectal cancer (CRC) worldwide. As sporadic CRC represents a typical multifactorial disease, it is characterized by intense interaction of the genetic background with the environment. Glutathione S-transferases could act as attractive susceptibility genes for CRC, as they are directly involved in conjugation between glutathione and chemotherapeutics, environmental pollutants and a wide spectrum of xenobiotics. Methods In this study, we investigated associations of polymorphisms in glutathione S-transferases ( GSTs ) genes, that is GSTA1 , GSTT1 , GSTM1 and GSTP1 , with CRC in a total of 197 cases and 218 controls originating from the Czech Central European population. Polymorphisms were assessed by polymerase chain reaction/restriction fragment length polymorphism-based methods, allele-specific multiplex and allelic discrimination by real-time polymerase chain reaction. Results None of investigated polymorphisms showed any associations with CRC, with the exception of GSTP1; where the heterozygote genotype Ile105Val was associated with decreased risk of CRC ( P = 0.043). Conclusions The frequencies observed in our study are in accordance with those from other European Caucasian populations. Based on our studies, examined variability in GST genes is not a major determinant of CRC susceptibility in the Central European population.

Sujets

• Colorectal cancer
• Glutathione S-transferase A1
• GSTT1
• Glutathione S-transferase Mu 1
• GSTP1
• Polymorphism

Informations

• Publié par: biomed
• Publié le: 01 janvier 2012
• Nombre de lectures: 8
• Langue: English

Extrait

Hezovaet al. European Journal of Medical Research2012,17:17 http://www.eurjmedres.com/content/17/1/17

R E S E A R C H

EUROPEAN JOURNAL OF MEDICAL RESEARCH

Open Access

Common polymorphisms inGSTM1, GSTT1, GSTP1, GSTA1and susceptibility to colorectal cancer in the Central European population 1 2,3 1 1 2 1 Renata Hezova , Julie BienertovaVasku , Milana Sachlova , Veronika Brezkova , Anna Vasku , Marek Svoboda , 5 1 1 1,4* Lenka Radová , Igor Kiss , Rostislav Vyzula and Ondrej Slaby

Abstract Background:Central Europe presents with the highest incidence of sporadic colorectal cancer (CRC) worldwide. As sporadic CRC represents a typical multifactorial disease, it is characterized by intense interaction of the genetic background with the environment. Glutathione Stransferases could act as attractive susceptibility genes for CRC, as they are directly involved in conjugation between glutathione and chemotherapeutics, environmental pollutants and a wide spectrum of xenobiotics. Methods:In this study, we investigated associations of polymorphisms in glutathione Stransferases (GSTs) genes, that isGSTA1,GSTT1,GSTM1andGSTP1, with CRC in a total of 197 cases and 218 controls originating from the Czech Central European population. Polymorphisms were assessed by polymerase chain reaction/restriction fragment length polymorphismbased methods, allelespecific multiplex and allelic discrimination by realtime polymerase chain reaction. Results:None of investigated polymorphisms showed any associations with CRC, with the exception ofGSTP1; where the heterozygote genotype Ile105Val was associated with decreased risk of CRC (P= 0.043). Conclusions:The frequencies observed in our study are in accordance with those from other European Caucasian populations. Based on our studies, examined variability inGSTgenes is not a major determinant of CRC susceptibility in the Central European population. Keywords:Colorectal cancer,GSTA1,GSTT1,GSTM1,GSTP1, Polymorphism

Background Colorectal cancer (CRC) represents the third most fre quent type of cancer among males and the second most common cancer in females worldwide. Worldwide, every year, more than 1 million individuals will develop colo rectal cancer and the diseasespecific mortality rate is nearly 33% in the developed world [1], making the dis ease a substantial health as well as economic burden on society. Sporadic CRC is a typical multifactorial disease arising from maladaptive interaction between genetic background and certain environmental factors, such as

* Correspondence: [e-mail] 1 Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Zluty kopec 7, 656 53, Brno, Czech Republic 4 Central European Institute of Technology, Masaryk University, Kamenice 753/5, 625 00, Brno, Czech Republic Full list of author information is available at the end of the article

diet or lifestyle, however, the exact role of the genetic background to sporadic CRC remains unclear. Glutathione Stransferases (GSTs) represent a superfamily of phase II metabolic enzymes that catalyze the conjugation between glutathione and chemotherapeutic drugs, carcino gens, environmental pollutants, and a broad spectrum of xenobiotics.GSTs are involved in the metabolism of isothia cyanates (ITCs), naturally occurring molecules that were re cently shown to inhibit development of tumors in many experimental models [2] and that also induce apoptosis in human colon cancer cells [3].GSTizoenzymes are encoded by three separate families of genes (designated cytosolic, microsomal and mitochondrial transferases), with distinct evolutionary origins, which provide mammalian species with protection against electrophiles and oxidative stressors in the environment. Members of the cytosolic class Alpha,

© 2012 Hezova et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.